the global role of kidney transplantation · donor kidney transplants and living donor recipients...

The global role of Kidney Transplantation

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The Global Role of Kidney Transplantation Guillermo Garcia Garcia1, Paul Harden2, Jeremy Chapman3 For the World Kidney Day Steering Committee 2012* 1 Nephrology Service, Hospital Civil de Guadalajara, University of Guadalajara Health Sciences Center (CUCS)Hospital 278,Guadalajara, Jal. 44280, MEXICO 2 Oxford Kidney Unit and Oxford Transplant Centre, Churchill Hospital, Oxford, United Kingdom 3 Centre for Transplant and Renal Research, Westmead Millennium Institute, Sydney University, Westmead Hospital, Sydney, NSW, 2145, Australia Address for correspondence: World Kidney Day, International Society of Nephrology, Rue des Fabriques 1, 1000 Brussels, Belgium. Email: [email protected] *World Kidney Day (WKD) is a joint initiative of the International Society of Nephrology and the International Federations of Kidney Foundations.

WKD Steering Committee members: Abraham G, Beerkens P, Chapman JR, Couser W,Erk T, Feehally J, Garcia GG, Li PKT, Riella M, Segantini L, Shay P.


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ABSTRACT (199words) World Kidney Day on March 8th 2012 provides a chance to reflect on the success of

kidney transplantation as a therapy for end stage kidney disease that surpasses dialysis

treatments both for the quality and quantity of life that it provides and for its cost

effectiveness. Anything that is both cheaper and better, but is not actually the

dominant therapy, must have other drawbacks that prevent replacement of all dialysis

treatment by transplantation. The barriers to universal transplantation as the therapy

for end stage kidney disease include the economic limitations which, in some countries

place transplantation, appropriately, at a lower priority than public health

fundamentals such as clean water, sanitation and vaccination. Even in high income

countries the technical challenges of surgery and the consequences of

immunosuppression restrict the number of suitable recipients, but the major finite

restrictions on kidney transplantation rates are the shortage of donated organs and

the limited medical, surgical and nursing workforces with the required expertise.

These problems have solutions which involve the full range of societal, professional,

governmental and political environments. World Kidney Day is a call to deliver

transplantation therapy to the one million people a year who have a right to benefit.


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INTRODUCTION

Kidney transplantation is acknowledged as a major advance of modern medicine which

provides high-quality life years to patients with irreversible kidney failure (end-stage

renal disease, ESRD) worldwide. What was an experimental, risky and very limited

treatment option fifty years ago, is now routine clinical practice in more than 80

countries. What wasonce limited to a few individuals in a small number of leading

academic centers in high income economies, is now transforming lives as a routine

procedure in most high- and middle-income countries – but can do much more. The

largest numbers of transplants are performed in the USA, China, Brazil and India, while

the greatest population access to transplantation is in Austria, USA, Croatia, Norway,

Portugal and Spain.There arestill many limitations in access to transplantation across

the globe. World Kidney Day on March 8th 2012 will bring focus to the tremendous life-

changing potential of kidney transplantation as a challenge to politicians, corporations,

charitable organizations and healthcare professionals. This commentary raises

awareness of the progressive success of organ transplantation, highlight concerns

about restricted community access and human organ trafficking and

commercialism,while also exploring the real potential for transforming kidney

transplantation intothe routine treatment option for ESRDacross the world.

Outcomes of kidney transplantation The first successful organ transplantation is widely acknowledged to be a kidney

transplant between identical twins performed in Boston on 23rd Dec 1954 which

heralded the start of a new era for patients with ESRD1.


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In the development years between 1965 and 1980, patient survival progressively

improved towards 90% and graft survival rose from less than 50% at one year to at

least 60% after a first deceased donor kidney transplant,based on immunosuppression

with azathioprine and prednisolone. The introduction of ciclosporin in the mid 1980s

was a major advance, leading to one year survival rates of more than 90% and graft

survival of 80%2.In the last 20 years, betterunderstanding of the benefits of combined

immunosuppressant drugs coupled with improved organ matching and preservation,

as well as chemoprophylaxis of opportunistic infections,have all contributed to a

progressive improvement in clinical outcomes.Unsensitised recipients of first deceased

donor kidney transplants and living donor recipients can now expect 1-year patient

and transplant survival to be at least 95% and 90% respectively1. New developments

have led several groups to report excellent results even from carefully selected ABO

Blood group incompatible transplants in recipients with low titre ABO-antibodies3.

Even for those with high titresof donor specific HLA-antibodies, who were previously

‘untransplantable,better de-sensitisation protocols4and paired kidney exchange

programs5 now afford real opportunities for successful transplantation.

Ethnic minorities and disadvantaged populations continue to suffer worse outcomes;

Aboriginal Canadians, for example, have lower 10-year patient (50% vs 75%) and graft

(26% vs 47%) survival compared with white patients6. African American kidney

transplant recipients have shorter graft survival compared to Asian, Hispanic, and

White populations in the United States of America7. In New Zealand,Maori and Pacific

Island recipients of deceased donor transplants have a 50% 8-year graft survival

compared to 14 years for non-indigenous recipients,in part due to differences


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inmortality8. By contrast,despite a resource poor environment, Rizvi et alreport 1 and

5-year survival rates of 92% and 85%, respectively, among 2,249 living related kidney

transplants in Pakistan9, whilst in Mexico, 90% and 80% one-year survival for living and

deceased donor kidney transplants, was reported among 1,356 transplants performed

at a single centre10. But, while it is possible to achieve such excellent long-term results,

most patients and their families in resource poor environments are not be able to

afford the high cost immunosuppressants and antiviral medications needed toreduce

the risk of graft loss and mortality11.

The place of kidney transplantation in treatment for ESRD

Kidney transplantation improves long-term survival compared to maintenance dialysis.In

46,164 patients on the transplant waiting list in the USA between 1991-1997, mortality

was 68% lower for transplant recipients than for those remaining on the transplant

waiting list after>3 yrs follow-up12. The transplanted 20-39 year old patients of both

sexes were predicted to live 17 years longer than those remaining on the transplant

waiting list, an effect that was even more marked in diabetics.

The number of people known to have ESRD worldwide is growing rapidly, as a result of

improved diagnostic capabilities and also the global epidemic of type 2 diabetes and

other causes of chronic kidney disease (CKD). Dialysis costs are expensive even for

developed countries, but prohibitive for many emerging economies. The majority of

patients commencing dialysis for ESRD in low-income countries die or stoptreatment

within the first 3 months of initiating dialysis due to cost restraints13. The cost of

maintenance hemodialysis varies considerably by country and healthcare system. In


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Pakistan maintenance hemodialysisis reported to be US$1680 per year, which is

beyond the reach of most of the population without humanitarian financial aid14.

Despite exemplars, both provision of hemodialysis facilities and uptake of peritoneal

dialysis remain very limited in middle and low-income countries. Whilst the costs of

transplantation exceed those of maintenance dialysis in the first year post-

transplantation (eg. in Pakistan US$5245vsUS$1680 in the first year), the costs are

much reduced compared to dialysis in subsequent years, especially with the advent of

inexpensive generic immunosuppression15.Transplantation thus expands access and

reduces overall costs for successful treatment of ESRD.

Pre-emptivetransplantationis an attractive option for both patients and payers with

both reduced costs and improved graft survival16 . . Pre-emptive transplantation is

associated with a 25% reduction in transplant failure and 16% reduction in mortality

compared to recipients receiving a transplant after starting dialysis17.

Transplantation of the kidney, when properly applied, is thus the treatment of choice

for patients with ESRDbecause of lower costs and better outcomes.

Global disparities in access to kidney transplantation

Substantial disparities in access to transplantation across the world are demonstrated

in Figure 1 (derived from the World Health Organisation/OrganisationMondiale de la

Sante (WHO/OMS) Global Observatory on Donation and Transplantation18). ) which

demonstrates the relationship between transplant rate and Human Development

Index (HDI). There is a reduced transplant rate in low and middle HDI countries, and a


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large spread of transplant rates even amongst the richer nations. Transplant rates of

more than 30 per million population (pmp) in 2010 were restricted to Western Europe,

USA, and Australia, with a slightly broader spread of countries achieving between 20

and 30 pmp.[NOTE for national journal versions add sentence here] [And then add an

arrow pointing to the particular position for that country on the figure]

There are also within-country disparities in transplant rates among minorities and

other disadvantaged populations. In Canada, all minority groups have significantly

lower transplant rates; compared to whites, rates in Aboriginal and African Canadians,

Indo Asians, and East Asians were 46%, 34%, and 31% lower respectively.19. In the US,

transplantation rates are significantly lower among African-Americans, women, and

the poor, compared to Caucasians, men and the more affluent populations20.The

situation is similar in Australia where Aboriginal Australians fare worse than non-

indigenous Australians (12% vs 45%) and in New Zealand where Maori/Pacific Islanders

are disadvantaged (14% vs 53%)21. In Mexico, the transplant rate among uninsured

patients is 7 pmp compared with 72 pmp among those with health insurance22.

Multiple immunologic and non-immunologic factors contribute to social, cultural, and

economic disparities in transplant outcomes, including biological, immune, genetic,

metabolic, and pharmacological factors as well as associated co-morbidities, time on

dialysis, donor and organ characteristics, patient socio-economic status, medication

adherence, access to care, and public health policies23. Developing countries often

have especially poor transplant rates not only because of these multiple interacting

factors,but also because of inferior infrastructure and an insufficient trained


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workforce. Deceased donation rates may also be impacted by lack of a legal

framework governing brain deathand by religious, cultural and social constraints.

When these factors are all compounded by patient anxieties about the success of

transplantation, physician bias, commercial incentives favoring dialysis and

geographical remoteness, poor access to transplantation is almost inevitable for most

of the world’s population.

Improving access to transplantation

Both living donation and deceased donor donation are now recognized by the WHOas

critical to the capacity of nations to develop self-sufficiency for organ

transplantation24. No country in the world, however, generates sufficient organs from

these sources to meet the needs of their citizens. Austria, USA, Croatia, Norway,

Portugal and Spainstand out as countries with high rates of deceased organ donors,

and most developed countries are trying to emulate their success. A return to

‘donation after cardiac death’ instead of the now standard ‘donation after brain

death’, has enhanced the deceased organ donation numbers in several countries, with

2.8DCD donorspmp in the US and 1.1pmp in Australia now emanating from this

source. Protocols for rapid cooling and urgent retrieval of kidneys after cardiac death,

and in some circumstances other organs, have developed over the past five years to

reduce the duration and consequences of warm ischaemia25. Another strategy for

increasing the rate of transplantation has been to extend the acceptance criteria for

deceased organ donors. Such ‘extended criteria’ donors require additional


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consideration and specific consent by the recipient. ,. There is risk in accepting an

‘extended criteria’ kidney since the transplants are less successful in the long term, but

also a risk to waiting longer on dialysis for a standard criteria donor.

A number of strategies have been designed and implemented to reduce disparities

among disadvantaged populations. The Transplantation Society has established the

Global Alliance for Transplantation in an effort to reduce worldwide disparities in

transplantation. The program includes collecting global information, expandingf

education about transplantation, and developing guidelines for organ donation and

transplantation. The International Society of Nephrology (ISN) Global Outreach

program has catalysed the development of kidney transplant programs across a large

number of countries with targeted fellowship training and creation of long term

institutional links between developed and developing transplant centers through its

Sister Center Program. This has led to the establishment of successful kidney

transplantation in countries such as Armenia ,Ghana and Nigeria where none existed

before and expansion of existing programs in Belarus, Lithuania and Tunisia.

A model of collaboration for dialysis and transplantation between government and the

community in the resource poor world has been successfully established in Pakistan

with government assistance for infrastructure, utilities, equipment, and up to 50% of

the operating budget, while the community, including affluent individuals,

corporations and the public, donate the remainder14. In 2001, in Central America, a

specialized unit of pediatric nephrology and urology was opened in Nicaragua with

funds provided initially by the Associazione per il Bambino Nefropatico, a kidney


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foundation based in Milan, Italy supplemented by a consortium of private and public

organizations, including the International Pediatric NephrologyAssociation and the

Nicaraguan Ministry of Health. Subsequently the Nicaraguan government and a local

kidney foundation recognized the success of the program and accepted gradual

transfer of the costs of treatment, including the provision of immunosuppressive

medications for renal transplantation. A similar successful partnership between

government and private sector has recently been reported in India26

There are tremendous opportunities to correct disparities in kidney disease and

transplantation worldwide, but it is important to recognize that funding of ESRD

treatment should be associated with funding for early detection and prevention of the

progressive kidney diseases that lead to ESRD. .Comprehensive programs should

include communityscreening and prevention of CKD, especially in high-risk

populations, as well as dialysis and transplantation for ESRD.

An integrated approach to the expansion of transplantation requires training programs

for nephrologists, transplant surgeons, nursing staff, and donor coordinators;

nationally funded organ procurement organizations providing transparent and

equitable retrieval and allocation; and the establishment of national ESRD registries.

Ethical challenges and the legal environment

The impact of the global organ donor shortage and the dramatic disparities

demonstrated by the WHO data, are experienced in many different ways requiring

variedresponses. But one common factor is the relative wealth of the nation and the


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individual. The poor receive the fewest transplants and the rich are most often

transplanted either in their own country or through finding an organ through illegal

purchase from the poor or an executed prisoner. Trafficking in human organs and

commercialisation of the beneficial act of organ donation were unusual and extremely

hazardous in the 1980’s, became frequent but still very hazardous in the 1990’s, then

becoming agruesomely burgeoning trade from the turn of the century. The WHO has

estimated that up to 10% of all organ transplants were of commercial origin by 200527.

The first WHO Guiding Principles in this field were agreed in 1991and made clear by

the decision of national governments to ban commercialization of organ donation and

transplantation28. This principle was reaffirmed unanimously by theWorld Health

Assembly in 2010 when the updated WHO Guiding Principles for human organ and

tissue donation and transplantation, were endorsed29. Almost all countries with

transplantation programs and even some without active programs have carried that

ban on commercialism through to their own legislation, making it illegal to buy or sell

organs. Sadly this has not prevented continuation of the trade illegally in countries

such as China and Pakistan, nor has it prevented new entrants to this lucrative trade

from taking advantage of their own or other nations’ impoverished and vulnerable

populations to provide kidneys and even livers for the desperate wealthy in need of

transplantation.

Iran, alone, claims to have resolved national self sufficiency for kidney transplantation

through a scheme of part government, part patient-funded sale of kidneys by vendors.

The resultant slow development of deceased organ donation in Iran restricting liver,


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heart and lung transplant programs, as well as the disparity of socioeconomic status

between donors and recipients, both testify to the universality of the problems that

arise from organ transplant commercialisation. The restriction of transplantation to

Iranian nationals only under this program has however largely ensured that this

national experiment has not flowed onto createcommercial organ trafficking across

Iranian national borders.

The Transplantation Society and the ISN have taken a joint stand against the despoiling

of transplantation therapy and victimization of the poor and vulnerable by doctors and

other providers operating in these illegal programs. In 2008, more than 150

representatives from across the world from different disciplines of health care,

national policy development, law and ethics came together in Istanbul to discuss and

define professional principles and standards for organ transplantation. The resultant

Declaration of Istanbul30 has now been endorsed by more than 110 professional and

governmental organizations and implemented by many of these organizations with a

goal to eliminate transplant tourism and enhance the ethical practice of

transplantation globally31.

Summary

There remain major challenges to providing optimal treatment for ESRD worldwide

and a need, particularly in low income economies, to mandate more focus on

community screening and implementation of simple measures to minimize progression

of CKD. The recent designation of renal disease as an important non-communicable

disease at the UN High Level Meeting on NCDs is one step in this direction32. But early


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detection and prevention programs will never prevent ESRD in everyone with CKD, and

kidney transplantation is an essential, viable, cost-effective and life-saving therapy

which should be equally available to all people in need. It may be the only tenable

long-term treatment option for ESRD in low-income countries since it is both cheaper

and provides a better outcome for patients than other treatment for ESRD.However,

the success of transplantation has not been delivered evenly across the world, and

substantial disparities still exist in access to transplantation, we remain troubled

bycommercialization of living donor transplantation and exploitation of vulnerable

populations for profit.

There are solutions available. These include demonstrably successful models of kidney

transplant programs in many developing countries; growing availability of less

expensive generic immunosuppressive agents; improved clinical training opportunities;

governmental and professional guidelines legislating prohibition of commercialization

and defining professional standards of ethical practice; and a framework for each

nation to develop self sufficiency in organ transplantationthrough focus on both living

donation and especially nationally managed deceased organ donation programs. The

ISN and TTS have pledged to work together in coordinated joint global outreach

programs to help establish and grow appropriate kidney transplant programs in low

and middle income countries utilizing their considerable joint expertise.World Kidney

Day 2012 provides a focus to help spread this message to governments, all health

authorities and communities across the world.


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32. UnitedNations General Assembly. Political declaration of the High-level Meeting of

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Figure:

Number of Deceased and Living Donor Kidney Transplants in World Health

Organisation Member States in 2010, correlated with Human Development Index.

Grouped by WHO Regions (AFR = Africa, AMR = Americas, EMR = Eastern

Mediterranean, EUR = Europe, SEAR = South Eastern Asia, WPR = Western Pacific)

Human Development Index

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the global role of kidney transplantation · donor kidney transplants and living donor recipients...

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